1. Involvement of Src kinases and PLCγ2 in clot retraction
- Author
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Toshiro Takafuta, Osamu Inoue, Yukio Ozaki, Makoto Kaneko, Olga Cuyun-Lira, Katsue Suzuki-Inoue, Steve P. Watson, and Craig E. Hughes
- Subjects
030204 cardiovascular system & hematology ,Fibrinogen ,PRP, platelet-rich plasma ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,PLCγ2, phospholipase Cγ2 ,Phosphorylation ,TBS-T, Tris-buffered saline/Tween 20 ,0303 health sciences ,Kinase ,digestive, oral, and skin physiology ,Regular Article ,Hematology ,ACD, acid/citrate/dextrose ,3. Good health ,Cell biology ,Platelet Glycoprotein GPIIb-IIIa Complex ,Integrin αIIbβ3 ,src-Family Kinases ,SLP-76, SH2-containing leucocyte phosphoprotein of 76 kDa ,Outside-in signal ,Src kinases ,Proto-oncogene tyrosine-protein kinase Src ,medicine.drug ,circulatory and respiratory physiology ,Signal Transduction ,Blood Platelets ,Myosin Light Chains ,PLCγ2 ,Integrin ,Clot Retraction ,Clot retraction ,macromolecular substances ,Biology ,In Vitro Techniques ,PP2, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo-d-3,4-pyrimidine ,Models, Biological ,03 medical and health sciences ,medicine ,Animals ,Humans ,mAb, monoclonal antibody ,Protein Kinase Inhibitors ,030304 developmental biology ,Phospholipase C gamma ,Tyrosine phosphorylation ,Molecular biology ,chemistry ,biology.protein - Abstract
The integrin alpha(IIb)beta(3) plays a critical role in mediating clot retraction by platelets which is important in vivo in consolidating thrombus formation. Actin-myosin interaction is essential for clot retraction. In the present study, we demonstrate that the structurally distinct Src kinase inhibitors, PP2 and PD173952, significantly reduced the rate of clot retraction, but did not prevent it reaching completion. This effect was accompanied by abolition of alpha(IIb)beta(3)-dependent protein tyrosine phosphorylation, including PLCgamma2. A role for PLCgamma2 in mediating clot retraction was demonstrated using PLCgamma2-deficient murine platelets. Furthermore, platelet adhesion to fibrinogen leads to MLC phosphorylation through a pathway that is inhibited by PP2 and by the PLC inhibitor, U73122. These results demonstrate a partial role for Src kinase-dependent activation of PLCgamma2 and MLC phosphorylation in mediating clot retraction downstream of integrin alpha(IIb)beta(3).
- Published
- 2007